Obesity is a major health problem worldwide. Brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays essential roles in the regulation of energy balance in many species including humans. Thus, BDNF system could be one of the therapeutic targets for prevention and treatment of obesity. There is increasing evidence that regulation of energy balance and metabolism is not the same for both genders. Previous studies suggest that BDNF activates sympathetic nervous system to regulate metabolism. However, the exact neural circuit responsible for BDNF-induced energy metabolism is unknown. Additionally, females are more sensitive to BDNF's effects on the regulation of energy balance than males. The underlying neural mechanism for the sex differences in energy metabolism regulated by BDNF is unknown. This project will examine potential neural mechanism of BDNF system in regulating energy metabolism in male and female rats. First, the central nervous system-peripheral tissue circuit involving BDNF will be identified. Then changes in specific sympathetic molecular markers and sympathetic drive to metabolic tissues by BDNF administration will be assessed. Collectively, this project will provide direct neuroanatomical, neurofunctional, molecular, and neurochemical evidence underlying the mechanisms of BDNF's effects on metabolism and energy homeostasis. Additionally, this project will provide important new information about sex differences in response to BDNF administration. Such information is invaluable for identifying gender-specific biological targets for intervention to prevent or treat obesity. Furthermore, this project provides plentiful opportunities for graduate and undergraduate students to participate in research and to enhance research environment at Miami University, in agreement with the R15 mission.